# US 8,771,743 B2 · Multi-layered lamellar granule and skin external application composition containing same

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- Number: US 8,771,743 B2
- Document ID: US8771743B2
- Status: Granted
- Kind: B2
- Application number: 13/055,091
- Filed: 2008-09-02
- Published: 2011-05-26
- Granted: 2014-07-08
- Earliest claimed: 2008-07-24
- Assignees: Amorepacific Corporation
- Applicants: Do Hoon Kim; Eun Jung An; Jae Sung Hwang; Hong Ju Shin; Won Seok Park; Chang Geun Yi; Jong Hee Park; Jeong Hwan Kim; Jin Woong Kim; Jung A Seo; Yong Jin Kim; Jong Won Shim; Mi Jin Kim
- Inventors: Do Hoon Kim; Eun Jung An; Jae Sung Hwang; Hong Ju Shin; Won Seok Park; Chang Geun Yi; Jong Hee Park; Jeong Hwan Kim; Jin Woong Kim; Jung A Seo; Yong Jin Kim; Jong Won Shim; Mi Jin Kim
- Web page: https://patentgrep.com/patent/US8771743B2

## CPC

- A61K 9/5078: {with drug-free core}
- A61K 8/0245: {Specific shapes or structures not provided for by any of the groups of A61K8/0241}
- A61K 8/68: Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/10: Dispersions; Emulsions
- A61P 17/00: Drugs for dermatological disorders
- A61Q 19/007: {Preparations for dry skin}
- A61K 2800/412: Microsized, i.e. having sizes between 0.1 and 100 microns
- A61K 2800/614: By macromolecular compounds
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

Provided are: a multi-layered lamellar granule comprising a nucleating agent, a ceramide-containing artificial stratum corneum lipid lamellar layer which encases the nucleating agent and a polymer layer disposed on the artificial stratum corneum lipid lamellar layer; and an external skin application composition comprising the same. The external skin application composition shows improved moisturizing and barrier repair capabilities when applied to the skin, which can be advantageously used in cosmetics and pharmaceuticals.

## Claims

### Claim 1

A multi-layered lamellar granule comprising:
a nucleating agent particle; and
a ceramide-containing artificial stratum corneum lipid layer, said artificial stratum corneum lipid layer having a multi-layered lamellar structure that is spray-coated on the nucleating agent particle and embeds the nucleating agent particle in the multi-layered lamellar structure,
wherein an outer surface of the multi-layered lamellar granule of the artificial stratum corneum lipid lamellar layer and the nucleating agent particle is spray-coated with a polymer layer; and
wherein the nucleating agent particle is a particle made of the substance selected from the group consisting of sugar, a salt, hyaluronic acid, alginic acid, chondroitin sulfate, chitosan, chitin, polylysine, collagen, gelatin, stearic acid, cetyl alcohol, stearyl alcohol, and a mixture thereof.

### Claim 2 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the amount of the nucleating agent is 1 to 99% by weight based on the total amount of the multi-layered lamellar granule.

### Claim 3 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the ceramide is a natural ceramide, a pseudoceramide, or a mixture thereof.

### Claim 4 (depends on 3)

The multi-layered lamellar granule of claim 3, wherein the natural ceramide is selected from the group consisting of ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, ceramide 7, ceramide 8, and a mixture thereof.

### Claim 5 (depends on 3)

The multi-layered lamellar granule of claim 3, wherein the pseudoceramide is selected from the group consisting of compounds of formulae (I) to (VI), and a mixture thereof:
wherein,
R is a saturated or unsaturated C9-C21 aliphatic chain moiety;
wherein,
n is 1 or 2; and
R and R′ are each a saturated or unsaturated C9-C21 aliphatic chain moiety;
wherein,
m and n are each independently an integer of 1 to 3;
k and l are each independently 1 or 2;
j is 0 or 1;
R and R′ are each independently a linear or branched, saturated or unsaturated C1-C31 hydrocarbon group, optionally having one or more hydroxyl substituents; and
A1, A2 and A3 are each independently hydrogen or one of following groups, with the proviso that A1, A2 and A3 are not simultaneously hydrogen:
wherein, M, M1 and M2 are each independently selected from the group consisting of an alkali metal, a lysine moiety, an arginine moiety, a histidine moiety, triethylammonium, ammonium, polyquaternium-4, polyquaternium-6, polyquaternium-7, polyquaternium-10, polyquaternium-11, polyquaternium-16, lauryldimethylbenzylammoniumchloride and stearyldimethylbenzylammoniumchloride, and L is an alkali earth metal;
wherein,
R and R′ are each independently a linear or branched, saturated or unsaturated C10-C32 hydrocarbon group, optionally having one or more hydroxyl substituents;
R3 and R4 are each independently hydrogen, C1-C4 alkyl, or C1-C4 hydroxyl alkyl; and
R5 is -A or —CH2CH2OA, wherein A is one of following groups;
wherein, M, M1 and M2 are each independently selected from the group consisting of an alkali metal, a lysine moiety, an arginine moiety, a histidine moiety, triethylammonium, ammonium, polyquaternium-4, polyquaternium-6, polyquaternium-7, polyquaternium-10, polyquaternium-11, polyquaternium-16, lauryldimethylbenzylammoniumchloride and stearyldimethylbenzylammoniumchloride, and L is an alkali earth metal;
wherein,
m and n are each independently an integer of 1 to 4;
R and R′ are each independently a linear or branched, saturated or unsaturated C1-C31 hydrocarbon group, optionally having one or more hydroxyl substituents;
A1 and A2 are each independently hydrogen or one of following groups:
wherein, M, M1 and M2 are each independently an alkali metal or a nitrogen-containing organic base, and L is an alkali earth metal;
wherein,
m and n are each independently an integer of 1 to 3;
k and l are each independently 1 or 2;
j is 0 or 1; and
A1, A2 and A3 are each independently hydrogen or one of following groups:
wherein, M, M1 and M2 are each independently an alkali metal or a nitrogen-containing organic base, and L is an alkali earth metal;
R is a substituent of following structure:
wherein, B is a methyl group in 5-, 7-, or 8-position of tocopherol; m is an integer of 1 to 3, and D is —CH2(CH3)—CH— or —CH(CH3)═C.

### Claim 6 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the amount of the artificial stratum corneum lipid lamellar layer is 0.00001 to 99% by weight based on the total amount of the multi-layered lamellar granule.

### Claim 7 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the artificial stratum corneum lipid lamellar layer further comprises a phospholipid, a fatty acid, a cholesterol or a derivative thereof, an alcohol, a molecular anchoring agent, or a mixture thereof.

### Claim 8 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the phospholipid is selected from the group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl glycerol, phosphatidyl inositol, phosphatidic acid, and a mixture thereof.

### Claim 9 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the fatty acid is a saturated or an unsaturated C8-C30 fatty acid.

### Claim 10 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the cholesterol or a derivative thereof is selected from the group consisting of cholesterol, cholesteryl chloride, cholesteryl octanoate, cholesteryl nonanoate, cholesteryl oleyl carbonate, cholesteryl isostearyl carbonate, and a mixture thereof.

### Claim 11 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the alcohol is a saturated or an unsaturated C8-C30 alcohol.

### Claim 12 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the molecular anchoring agent has a C12-C20 alkyl or alkenyl group as a hydrophobic moiety and a succinimidyl ester group as a hydrophilic moiety.

### Claim 13 (depends on 12)

The multi-layered lamellar granule of claim 12, wherein the molecular anchoring agent is an oleyloxy-poly(ethylene glycol)n-succinyl-N-hydroxysuccinimidyl ester, wherein n is an integer of 2 to 100.

### Claim 14 (depends on 7)

The multi-layered lamellar granule of claim 7, wherein the amount of the phospholipid, fatty acid, cholesterol or derivative thereof, alcohol, and molecular anchoring agent is 1-100 parts by weight, 1-100 parts by weight, 1-50 parts by weight, 1-50 parts by weight, and 1-50 parts by weight, respectively, based on 100 parts by weight of ceramide.

### Claim 15 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the amount of the polymer layer is 0.01 to 90% by weight based on the total amount of the multi-layered lamellar granule.

### Claim 16 (depends on 1)

The multi-layered lamellar granule of claim 1, wherein the multi-layered lamellar granule is prepared using a fluid-bed coater.

### Claim 17 (depends on 1)

An external skin application composition comprising the multi-layered lamellar granule of claim 1.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the amount of the multi-layered lamellar granule is 0.01 to 99% by weight based on the total amount of the composition.

### Claim 19 (depends on 17)

The composition of claim 17, wherein the composition is a cosmetic composition or a pharmaceutical composition.